HDR Endorectal Brachytherapy With 3D-Printed Guidance and Local Shielding for Rectal Cancer Organ Preservation

A Prospective Single-Arm Phase II Study of Pelvic External Beam Radiotherapy Followed by HDR Endorectal Brachytherapy Combined With a 3D-Printed Individualized Guide Template and Tungsten-Alloy Local Shielding for Organ Preservation in Inoperable Localized Rectal Cancer

This prospective, single-center, single-arm phase II study will evaluate the efficacy, safety, and technical feasibility of an organ-preserving radiotherapy strategy for patients with localized rectal adenocarcinoma who are medically inoperable, decline radical surgery, or are considered technically unresectable without distant metastases.

Participants will receive pelvic external beam radiotherapy followed by high-dose-rate (HDR) endorectal brachytherapy. Concurrent capecitabine may be given during external beam radiotherapy to participants who are considered able to tolerate chemotherapy. During HDR brachytherapy, all participants will be treated using a patient-specific 3D-printed guide template and individualized tungsten-alloy local shielding. The guide template is designed to improve applicator positioning and treatment reproducibility, while the local shielding is intended to reduce radiation exposure to non-target rectal wall.

The study will enroll 50 participants. The primary objectives are to evaluate the 12-month clinical complete response rate and the technical completion rate of the HDR brachytherapy platform. Secondary assessments include organ preservation, local regrowth, survival outcomes, treatment-related toxicity, quality of life, and anorectal function.

This investigator-initiated study is a prospective, open-label, single-arm phase II trial evaluating a definitive non-operative treatment strategy for localized rectal cancer. Eligible participants will have histologically confirmed rectal adenocarcinoma without distant metastases and will be considered medically unsuitable for radical surgery, decline radical surgery after appropriate counseling, or be considered technically unresectable by multidisciplinary assessment.

Following baseline evaluation and multidisciplinary review, participants will receive pelvic external beam radiotherapy. The planned dose to the pelvic planning target volume is 45 Gy in 25 fractions. Radiologically positive or highly suspicious lymph nodes will receive a simultaneous integrated boost to 55 Gy in 25 fractions, with escalation to 58-58.25 Gy in 25 fractions permitted when considered dosimetrically safe. Concurrent capecitabine at 825 mg/m² twice daily on radiotherapy days may be administered to participants who are considered able to tolerate chemotherapy; concurrent chemotherapy is not mandatory in this study.

Participants will undergo reassessment approximately 4-6 weeks after completion of external beam radiotherapy before proceeding to HDR endorectal brachytherapy. The planned HDR boost is 6 Gy per fraction for 3 fractions using an iridium-192 source, with fractions generally separated by 5-7 days.

During all HDR fractions, a patient-specific 3D-printed guide template will be used for applicator positioning, fixation, and reproducibility. Individualized flexible tungsten-alloy shielding, typically approximately 3 mm thick, will be positioned within a predefined channel in the template before treatment. The shielding configuration will be individualized according to tumor distribution and the location of non-target rectal wall requiring protection. Because the shielding material may produce substantial computed tomography artifacts, treatment planning will be performed before placement of the tungsten-alloy shielding, followed by verification of shielding direction, depth, and fixation before irradiation.

Tumor response will be assessed using a combination of digital rectal examination, endoscopy, and pelvic magnetic resonance imaging. Participants achieving a clinical complete response will enter a structured watch-and-wait follow-up program. Participants with residual disease, local regrowth, or progression will undergo multidisciplinary reassessment for individualized salvage treatment when appropriate.

In addition to clinical response and organ-preservation outcomes, the study will prospectively evaluate treatment-related toxicity and the technical performance of the individualized brachytherapy platform, including treatment completion, geometric reproducibility, shielding implementation, and dosimetric parameters.

Inclusion Criteria:

1. Age 18-80 years.
2. Histologically confirmed rectal adenocarcinoma.
3. Clinical stage cT2-4, any N, M0.
4. Patients who are elderly or frail, medically unsuitable for radical surgery, refuse radical surgery, or are considered by a multidisciplinary team (MDT) to have disease for which safe R0 resection is technically difficult.
5. Considered by the MDT and investigators to be suitable for a definitive non-operative treatment strategy.
6. ECOG performance status 0-2; patients with ECOG performance status 3 may be eligible if considered by the MDT to be able to tolerate the study treatment.
7. Estimated life expectancy of at least 6 months.
8. Considered suitable for pelvic external beam radiotherapy and HDR endorectal brachytherapy.
9. Tumor location, endorectal access, and local anatomy suitable for HDR brachytherapy using the individualized 3D-printed guide template.
10. Adequate hematologic, hepatic, and renal function for the planned treatment.
11. Ability to understand the study requirements and provide written informed consent.

Exclusion Criteria:

1. Distant metastatic disease or disease considered unsuitable for definitive local non-operative treatment.
2. Prior definitive pelvic radiotherapy.
3. Intestinal perforation, complete bowel obstruction, uncontrolled active bleeding, or severe active infection.
4. Anatomical or clinical conditions precluding HDR endorectal brachytherapy or use of the individualized guide template/local shielding platform.
5. Inflammatory bowel disease.
6. Severe uncontrolled cardiopulmonary disease, significant bone marrow suppression, or severe hepatic or renal dysfunction.
7. Pregnancy or breastfeeding.
8. Concurrent participation in another clinical trial that may interfere with evaluation of the study treatment or endpoints.
9. Any other condition considered by the investigator to make the patient unsuitable for participation in the study.